Positive Rate Of Estrogen Receptor Research Articles

Quality Assessment of Proteins and RNA Following Storage in Archival Formalin-Fixed Paraffin-Embedded Human Breast Cancer Tissue Microarray Sections.

Although the immunogenicity of formalin-fixed paraffin-embedded tissue sections can decrease during storage and transport, the exact mechanism of antigenic loss and how to prevent it are not clear. Herein, we investigated changes in the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), E-cadherin, and Ki-67 in human breast tissue microarray (TMA) tissue sections stored for up to 3 months in dry and wet conditions. The positive rates of ER and PR expression were minimally changed after 3 months of storage, but the Allred scores of ER and PR stored in humid conditions decreased remarkably in comparison to fresh-cut tissue. The HER-2 antigenicity and RNA integrity of breast TMA sections stored in dry conditions diminished gradually with storage time, whereas the immunoreactivity and RNA quality of HER-2 in humid conditions decreased sharply as storage length increased. The area and intensity of E-cadherin staining in tissue sections stored in dry conditions did not change significantly and were minimally changed after 3 months, respectively. In contrast, the area and intensity of E-cadherin staining in tissue sections stored in humid conditions decreased significantly as storage length increased. Finally, the Ki-67 labeling index of tissue sections stored for 3 months in dry (9% decrease) and wet (31.9% decrease) conditions was decreased in comparison to fresh sections. In conclusion, these results indicate that water is a crucial factor for protein and RNA degradation in stored tissue sections, and detailed guidelines are required in the clinic.

Analysis of the Clinical Molecular Characteristics and Neoadjuvant Chemotherapy Response in Patients with Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer and Axillary Lymph Node Metastasis

Objective: This study aimed to investigate the clinical molecular characteristics in patients with human epidermal growth factor receptor 2 (HER2)-negative breast cancer and axillary lymph node metastasis and explored the related factors of the neoadjuvant chemotherapy (NAC) response. Methods: The data of 185 patients with HER2-negative breast cancer and axillary lymph node metastasis who were treated in the Department of Breast Center of the Affiliated Hospital of Qingdao University from July 2017 to July 2021 were retrospectively analyzed. The clinical features and the related factors for the responses of the primary tumor and axillary lymph node metastasis to NAC were analyzed. Statistical analysis was conducted using the SPSS 26.0 statistical software. Univariate analysis was conducted using the χ2 test, and multivariate analysis was conducted using logistic regression analysis. Results: The differences in estrogen receptor (ER), progesterone receptor (PR), and Ki67 among the three HER2-negative subgroups (the immunohistochemistry (IHC)0 group, IHC1+ group, and IHC2+/in situ hybridization– group) were statistically significant (p < 0.05). Univariate analysis revealed that the differences in the tumor stage, ER, PR, and Ki67 among the groups based on the response of the primary tumor to NAC were statistically significant (p < 0.05), and the differences in ER, PR, and Ki67 among the groups based on the response of axillary lymph node metastasis to NAC were statistically significant (p < 0.05). Multivariate analysis revealed that the difference in Ki67 among the groups based on the response of axillary lymph node metastasis to NAC was statistically significant (p < 0.05). Conclusions: When the expression level of HER2-negative IHC increases, the positive rates of ER and PR increase. A smaller tumor, negative ER, negative PR, and a Ki67 level >30% indicate a good effect of NAC for primary tumors. Negative ER, negative PR, and a Ki67 level >30% indicate a good effect of NAC for axillary lymph node metastasis. Therefore, Ki67 may be an independent factor affecting the efficacy of NAC for axillary lymph node metastasis.

The Effect of Body Mass Index on Initial Breast Cancer Stage Among Korean Women

BackgroundThe relationship between obesity and breast cancer stage is not well-known in the Korean population. This study aimed to identify the effect of body mass index (BMI) on initial breast cancer stage. Patients and MethodsAmong patients who underwent surgery for breast cancer (stages 0-III) from June 2003 to December 2018, we analyzed 4510 patients for whom there were BMI data. ResultsThe average BMI of our patients was 23.5 (14.2-44.9). In total, 4.6% and 24.2% of the patients had a BMI of ≥30 and 25-29.9, respectively. In the patients with obesity, the proportion of T2 to T4 was 41.4%, which was higher than that in patients with a BMI of 25 to 29 (28.4%; P = .001) or a BMI of <25 (23.3%; P < .001). There was no difference in positive rates of estrogen receptor and progesterone receptor with BMI, but obese patients were less likely to be human epidermal growth factor receptor 2 positive. Patients with higher stages were more likely to have a higher BMI. The effect of BMI on stage was stronger in patients <50 years (odds ratio, 2.439; 95% CI, 1.783-3.335). Although there was no statistical significance, tumors >2 cm were less likely to be palpable in obese patients than in patients of normal weight (nonpalpable in 33.8% and 27.0%, respectively). ConclusionOur study suggests that obesity is associated with a more advanced breast cancer stage, which represents a poor prognosis, and large tumors tend to be less palpable in women with obesity.

Variability in Breast Cancer Biomarker Assessment and the Effect on Oncological Treatment Decisions: A Nationwide 5-Year Population-Based Study.

Simple SummaryBiomarkers that define breast cancer treatment recommendations include estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth-factor receptor 2 (HER2); histological grade; and in many countries, the Ki67 proliferation index. However, the subjective nature and degree of variability in breast cancer biomarker assessment might result in under- or overtreatment. We demonstrated that limited variability exists in ER, PR, and HER2 positivity rates among 29 departments in Sweden, including 43,261 patients. However, even a few outlier labs affect endocrine and anti-HER2 treatment rates in a clinically relevant proportion, indicating a need for improvement. Despite international guidelines, standardized protocols, and external quality control procedures, very high variability was found in Ki67 scoring and histological grading, indicating a need for new methods. Monitoring rates of biomarker expression and treatments among departments should be mandatory in order to detect variability issues affecting the clinical management of breast cancer.We compared estrogen receptor (ER), progesterone receptor (PR), human epidermal growth-factor receptor 2 (HER2), Ki67, and grade scores among the pathology departments in Sweden. We investigated how ER and HER2 positivity rates affect the distribution of endocrine and HER2-targeted treatments among oncology departments. All breast cancer patients diagnosed between 2013 and 2018 in Sweden were identified in the National Quality Register for Breast Cancer. Cases with data on ER, PR, HER2, Ki67, grade, and treatment were selected (43,261 cases from 29 departments following the guidelines for biomarker testing). The ER positivity rates ranged from 84.2% to 97.6% with 6/29 labs out of the overall confidence intervals (CIs), while PR rates varied between 64.8% and 86.6% with 7/29 labs out of the CIs. HER2 positivity rates ranged from 9.4% to 16.3%, with 3/29 labs out of the overall CIs. Median Ki67 varied between 15% and 30%, where 19/29 labs showed significant intra-laboratory variability. The proportion of grade-II cases varied between 42.9% and 57.1%, and 13/29 labs were outside of the CI. Adjusting for patient characteristics, the proportion of endocrine and anti-HER2 treatments followed the rate of ER and HER2 positivity, illustrating the clinical effect of inter- and intra-laboratory variability. There was limited variability among departments in ER, PR, and HER2 testing. However, even a few outlier pathology labs affected endocrine and HER2-targeted treatment rates in a clinically relevant proportion, suggesting the need for improvement. High variability was found in grading and Ki67 assessment, illustrating the need for the adoption of new technologies in practice.

Concordance of Hormone Receptor Status and BRCA1/2 Mutation Among Women With Synchronous Bilateral Breast Cancer.

Goals: BRCA1/2 mutations are associated with bilateral breast cancer. The extent of concordance between synchronous bilateral breast cancer (SBBC) tumors with respect to hormone receptor expression and BRCA1/2 mutations is unknown. We investigated the distribution of BRCA1/2 mutations and bilateral estrogen receptor (ER) status in SBBC.Methods: A retrospective analysis was performed on 15,337 patients with primary breast cancer who underwent surgical treatment at the Fudan University Shanghai Cancer Center between 2007 and 2014. We included 163 patients with synchronous bilateral breast cancer who had germline BRCA1/2 mutations testing. BRCA1/2 pathogenic/likely pathogenic mutations and other clinicopathological characteristics were studied in further analyses.Results: Patients with SBBC developed breast cancer at an older age and had a higher rate of ER positivity than patients with UBC (p < 0.001, separately). In contrast, 14.1% of SBBC patients had carcinomas with a lobular component in either breast based on pathological reports (p < 0.001). Twelve patients had BRCA1 mutations, and 14 patients had BRCA2 mutations, while no patients had mutations in both genes. The BRCA1/2 mutation rate was higher in younger patients (23.4 vs. 11.1%, p = 0.036). SBBC patients with a family history of breast cancer or bilateral ER-negative disease had a higher frequency of BRCA1/2 mutations than the cohort without a history of these conditions. SBBC with a bilateral ER-discordant status had a very low frequency of BRCA1/2 mutations (5.6%). Patients with an ER-positive (concordant or discordant) status had better 3-year disease-free survival than patients with a concordant ER-negative status (HR = 0.324, 95% CI: 0.126–0.837, P = 0.020). However, the outcomes were similar during long-term follow-up. Pathological lymph node stage was the only prognostic factor for SBBC in both univariate and multivariate Cox analyses.Conclusions: Our study shows that Chinese women with SBBC have different characteristics from their UBC counterparts. SBBC patients with a younger age, family history of breast cancer, or bilateral ER-negative disease are more likely to have BRCA1/2 mutations. SBBC patients with a concordant ER-negative status had worse early outcomes. Our results suggest that there may be additional factors underlying the tumor biology and genetics of SBBC.

The correlation between mammographic densities and molecular pathology in breast cancer

This study aimed to analyze the correlation between mammographic density obtained by density analysis software (DAS)/radiologists visual (RV) classification with molecular subtype, and the expression levels of estrogen receptor (ER), progesterone receptor (PR), Ki67 antigen (Ki-67), p53 gene (p53), and human epidermal growth factor receptor-2 (HER2). A total of 688 breast cancer patients with digital mammography and complete molecular pathological results in Tianjin Medical University Cancer Institute and Hospital between February 2015 and February 2016 were collected. The DAS-density grade (DASD) and the radiologists visually classified density grade (RVD) were evaluated by 3 radiologists. The correlation between density grade and the expression levels of ER, PR, Ki-67, p53, HER2 and breast cancer molecular subtype (PMS) were analyzed. The agreement between DASD and RVD was explored. ER, PR and HER-2 positive rate were significantly different among patients with different RVD grades (P< 0.05). HER2 positive rates showed an increasing trend following RVD upgrading (P𝑡𝑟𝑒𝑛𝑑< 0.05). HER-2 positive rate in RVD D1 + D2 was 7.69%, which was higher than that in D3 + D4 (P< 0.05). The ER and Ki-67 expressions in patients were markedly different among DASD (P= 0.009 and 0.002) and RVD (P= 0.012 and 0.036) with different grades. The kappa value of each DASD to RVD was 0.31 (P< 0.01). The RVD 3 proportion was 14.58% (63/432) in HER2 Over-expressing subtype, which was apparently higher than RVD1 (2.43%, 1/41) (P< 0.05). Breast density may be partial correlated with molecular pathology in breast cancer.

MRI findings and pathological features of occult breast cancer

Objective: To investigate the magnetic resonance imaging (MRI) findings and clinicopathological features of primary lesions in patients with occult breast cancer (OBC). Methods: The imaging reports from the Breast Imaging Reporting and Data System in 2013 were retrospectively analyzed to investigate the morphology and the time signal intensity curve (TIC) of breast lesions in patients with OBC. The clinical and pathological characteristics of these patients were also included. Results: A total of 34 patients were enrolled. Among these patients, 24 patients underwent modified radical mastectomy and 18 of them had primary breast carcinoma in pathological sections. MRI detected 17 cases of primary lesions, including six masse lesions with a diameter of 0.6-1.2 cm (average 0.9 cm), and 11 non-mass lesions with four linear distributions, three segmental distributions, three focal distributions, and one regions distribution. Five patients had TIC typeⅠprimary lesions, ten had TIC type Ⅱ primary lesions, and two had TIC type Ⅲ primary lesions. Among all 34 cases, 23 of them had complete results of immunohistochemistry: 11 estrogen receptor (ER) positive lesions (47.8%), tenprogesterone receptor (PR) positive lesions (43.5%), seven human epidermal growth factor receptor 2 (HER-2) positive lesions (30.4%), and 20high expression(>14%) of Ki-67 (87.0%). The proportion of type luminal A was 4.3%, type luminal B was 43.5%, triple negative breast cancer (TNBC) was 30.4%, and HER-2 over expression accounted for 21.7%. Conclusions: The primary lesions of OBC usually manifested as small mass lesions, or focal, linear or segmental distribution of non-mass lesions. The positive rate of ER and PR was low, but the positive rate of HER-2 and the proliferation index of Ki-67 was high. Type luminal B is the most common molecular subtype.

Effect of neoadjuvant chemotherapy on the expression of hormone receptors and Ki-67 in Chinese breast cancer patients: A retrospective study of 525 patients.

This study was designed to investigate the effect of neoadjuvant chemotherapy on the expression of hormone receptors and Ki67 in Chinese female breast cancer patients. The expression of estrogen receptor (ER), progesterone receptor (PR) and Ki67 among 525 neoadjuvant chemotherapy cases was studied by immunohistochemistry. Differences between specimens made through preoperative core needle biopsy and excised tissue biopsy were observed. The positive rates of ER, PR and Ki67 in core needle biopsy and excised tissue biopsy were 65.3% and 63.2%, 51.0% and 42.6%, 65.6% and 43.4%, respectively. The expression of ER, PR and Ki67 in core needle biopsy and excised tissue biopsy had no statistically significant difference. However, after neoadjuvant chemotherapy, the discordance rates of ER, PR and Ki67 were 15.2% (79/521), 26.9% (140/520) and 44.8% (225/502), respectively. The ER, PR and Ki67 status changed from positive to negative in 7.5% (39/521), 13.3% (69/520) and 21.1% (106/502) of the patients, whereas ER, PR and Ki67 status changed from negative to positive in 7.7% (40/521), 13.6% (71/520) and 23.7% (119/502) of the patients, respectively. These results showed that the status of some biomarkers changes after neoadjuvant chemotherapy and biomarker status needs to be reexamined to optimize adjuvant systemic therapy and better prognosis assessment.

The expression of ER, PR in endometrial cancer and analysis of their correlation with ERK signaling pathway.

Endometrial carcinoma (EC) is a common malignant tumor in gynecology. Its incidence and development are closely associated with the levels of estrogenic and progesterone hormone. Extracellular signal-regulated kinase (ERK) signaling pathway abnormity is associated with a variety of tumors. This study detected estrogen receptor (ER), progesterone receptor (PR), ERK1, and ERK2 expression in EC and analyzed their correlations. A total of 40 EC patients in our hospital were selected as test group, while another 40 healthy volunteers were enrolled as control group. ER, PR, ERK1, and ERK2 expression in EC tissue, para-carcinoma tissue, and normal endometrial tissue were detected by immunohistochemistry and Western blot. The positive rate of ER, PR, ERK1, and ERK2 in the test group was 50%, 40%, 60%, and 65%, respectively, which were significantly higher than those in the control (P< 0.05). ER, PR, ERK1, and ERK2 protein expressions in EC cell were significantly higher than those in the control (P< 0.05). ERK1 and ERK2 presented positive correlation with ER and PR (P< 0.05). In conclusion, EC patients presented higher expressions of ER, PR, which were correlated with higher levels of ERK1 and ERK2, suggesting they might be involved in the pathogenesis of EC.

Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 status of breast cancers in women visiting the Jos University Teaching Hospital

Introduction: Breast cancer remains the most common malignancy in women and the leading cause of morbidity and mortality in this gender. The disease in the indigenous African woman is associated with an inherent aggressive biology and worst clinical outcome. As the malignancy is a heterogeneous entity, each case must be individually categorized for efficient therapy. Current clinical practice employs the use of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), as biomarkers to appropriately select patients that would benefit from targeted therapy against these major molecular pathways of the disease. This study aims at establishing the ER, PR, and HER2 status of breast cancer in women visiting the Jos University Teaching Hospital. Materials and Methods: All histologically confirmed cases of breast cancer at the Jos University Teaching Hospital, between January 1, 2010, and December 31, 2012, with sufficient clinical records, were subjected to immunohistochemistry for the ER, PR, and HER2 status. Results: A total of 96 cases of female breast cancers were histologically diagnosed during the period of the study. Sixty-three (65.6%) cases met the inclusion criteria. The predominant histological type was invasive carcinoma (no special type) accounting for 54 (85.7%) cases. Scarf Bloom Richardson Grade 1, 2, and 3 for the cancer cases were: 18 (28.6%), 29 (46.0%), and 16 (25.4%), respectively. The rate of ER, PR, and HER2 positivity were 36.5%, 28.6%, and 33.3%, respectively. There were 26 (41.3%) triple-negative cases. Conclusion: The study shows a relatively low rate of hormone-receptor positivity, and higher HER2 positivity of breast cancers in our locality, which may be responsible for poor prognosis in our patients.

The clinical and pathological characteristics of breast cancer in women ≤40 years of age

Objective To retrospectively analyze the clinical and pathological characteristics of breast cancer in women ≤40 years of age. Methods One hundred and thirty one young (≤40 years) female patients with breast cancer pathologically confirmed in the General Hospital of PLA from January 1st 2008 to December 31st 2012 (young group) were collected, and 262 elderly (41-69 years) female patients with breast cancer in the same period (old group) were collected as control using the random number table method. The clinicopathological characteristics involved TNM staging, histological grade, the expression levels of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (Her-2) and clinical stage of the two groups were contrastively analyzed. Results Compared with elderly patients, young female patients with breast cancer had lower positive rate of ER or PR (64.9% vs. 76.7%; χ2=6.171, P=0.013), higher positive rate of Her-2 (26.7% vs. 15.3%; χ2=7.415, P=0.006) and higher histological grade (grade Ⅱ 38.2% vs. 35.1%; grade Ⅲ 55.7% vs. 49.6%; χ2=6.835, P=0.033). There were no significant differences in T stage (χ2=1.764, P=0.623), N stage (χ2=0.129, P=0.988), clinical stage (χ2=4.916, P=0.178), molecular subtype (χ2=7.475, P=0.058) and different surgical procedures (χ2=0.913, P=0.339) between the two groups. Conclusion Young (≤40 years) female patients with breast cancer have specific clinical and pathological characteristics including higher histological grade, higher positive rate of Her-2, lower positive rate of ER or PR and higher degree of malignancy, who should be diagnosed and treated as soon as possible. Key words: Breast neoplasms; Pathology, clinical

The clinical significance research between leptin, estrogen, estrogen receptor and lung adenocarcinoma

Objective To study the expressions and significances of leptin, estrogen and estrogen receptor (ER) in pulmonary squamous carcinoma and adenocarcinoma. Methods The expressions of leptin and estrogen receptor were detected in 58 cases of lung adenocarcinoma and 63 cases of pulmonary squamous cell carcinoma and 50 cases of normal lung tissue samples by immunohistochemical menthod, the levels of estrogen were also detected in patients with venous blood at the same time. Comparison of differential expression of leptin, estrogen and estrogen receptor in lung adenocarcinoma and lung squamous cell carcinoma, normal tissues, and explore their relationships with lung adenocarcinoma. Results Leptin, estrogen and estrogen receptor positive rates in lung adenocarcinoma group were 65.5%, 36.2% and 58.6% respectively, and 33.3%, 15.9%, 30.2% in lung squamous cell carcinoma group. There were a statistical difference between the two groups (χ2=4.324, P<0.050; χ2=5.372, P<0.050; χ2=5.718, P<0.050). In the normal control group the positive rates were 24.0%, 4.0% and 0 respectively, and there was a statistical difference compared with lung adenocarcinoma group (χ2=7.126, P<0.010; χ2=9.683, P<0.005; χ2=22.308, P<0.005). In lung adenocarcinoma group, leptin, estrogen and estrogen receptor positive rate have no relationships with tumor stage (χ2=0.001, P=0.950; χ2=0.061, P=0.900; χ2=0.178, P=0.750) and primary tumor size (χ2=0.023, P=0.900; χ2=0.001, P=0.950; χ2=0.001, P=0.950). Conclusion Leptin, estrogen and ER were expressed highly in adenocarcinoma of lung tumor. The expressions of leptin, estrogen and ER may associated with the carcinogenesis, development and clinical type of adenocarcinoma of lung. Key words: Leptin; Estrogens; Receptors, estrogen; Adenocarcinoma, bronchiolo-alveolar

Clinicopathological Characteristics and Survival Outcomes of Invasive Cribriform Carcinoma of Breast: A SEER Population-Based Study.

Invasive cribriform carcinoma (ICC) is a rare histologic subtype of breast cancer. We aimed to investigate the clinicopathological characteristics and survival outcomes of ICC.Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified 233,337 female patients diagnosed with ICC (n = 618) or infiltrating ductal carcinoma (IDC) (n = 232,719). Univariate and multivariate survival analyses were utilized to calculate and compare disease-specific survival (DSS) and overall survival (OS). A 1:1 paired match was carried out on age, tumor stage, tumor grade, estrogen receptor (ER) status, and progesterone receptor (PR) status. Baseline characteristics and survival outcomes were also analyzed in ER-positive tumors. Subgroup analyses summarized the hazard ratio (HR) of IDC versus ICC using a forest plot.ICCs presented smaller size, lower grade, higher ER and PR positive rate, less nodal metastasis, and were less likely to be treated with mastectomy compared to IDCs. Five-year DSS rates were significantly better for patients with ICC than for patients with IDC (98.8% vs. 93%, P < 0.001). Five-year OS rates were 95.3% versus 90.1% (P < 0.001). After adjustment for common clinicopathological factors in the multivariate analysis, patients with ICC showed limited DSS advantage over the IDC group (HR = 0.75, 95% CI: 0.38-1.51, P = 0.421). No significant difference in DSS nor OS was observed in matched groups between ICC and IDC. Analysis among ER-positive patients revealed similar prognostic factors as among all patients. Survival analysis in different tumor grade subgroups showed no significant difference between ICC and IDC.ICCs have unique clinicopathological characteristics, higher rates of breast-conserving surgery, and more favorable prognosis compared to the overall IDC population. Difference in tumor grade between the 2 groups may partially explain the different outcome. Improved clinical and biological understanding of ICC might lead to more individualized and tailored therapy for breast cancer patients.

Significance of mutant p53, Ki-67, ER and PR in differential diagnosis of uterine endometrial carcinoma and uterine serous carcinoma

Objective To investigate the expression of mutant p53, Ki-67, ER and PR in uterine endometrial carcinoma and uterine serous carcinoma, and explore their significance in differential diagnosis. Methods The samples including 37 cases of uterine endometrial carcinoma and 37 cases of uterine serous carcinoma were analyzed. The expression of mutant p53, Ki-67, estrogen receptor and progesterone receptor were performed by using the immunocytochemical (IHC) EnVision system. Data were analyzed with SPSS 11.5 statistic software. Results The positive rate of mutant p53 in uterine endometrial carcinoma was statistically lower than that in uterine serous carcinoma [21.62 % (8/37) vs 64.86 % (24/37) (P<0.01)]. The positive rate of Ki-67 in uterine endometrial carcinoma was statistically lower than that in uterine serous carcinoma [37.84 % (14/37) vs 70.27 % (24/37) (P<0.01)]. The positive rate of estrogen receptor in uterine endometrial carcinoma was statistically higher than that in uterine serous carcinoma [78.38 % (29/37) vs 32.43 % (12/37) (P<0.01)]. The positive rate of progesterone receptor in uterine endometrial carcinoma was statistically higher than that in uterine serous carcinoma [75.67 % (28/37) vs 29.73 % (11/37) (P<0.01)]. Conclusions The expression of mutant p53 and Ki-67 are higher in uterine serous carcinoma. The expression of estrogen receptor and progesterone receptor are higher in uterine endometrial carcinoma. Combined detection of mutant p53, Ki-67, ER and PR has important significance in screening and preventing uterine endometrial carcinoma and uterine serous carcinoma. Key words: Endometrioid carcinoma; Uterine serous carcinoma; p53; Ki-67; ER; PR; Differential diagnosis

Abstract P3-06-49: Prognostic impact of discordance in hormone receptor status after the neoadjuvant chemotherapy in primary breast cancer

Abstract Background: Hormone receptor (Estrogen receptor (ER), Progesterone receptor (PgR)) is an important biological marker for predicting prognosis and making effective treatment decisions. Discordance in these biomarkers between the primary tumor and recurrent lesions is reported frequently. However, it is not well known whether these biomarkers are affected by neoadjuvant chemotherapy and their impacts on outcomes still remain to be elucidated. The aim of the present study is to evaluate the changes in HR status after neoadjuvant chemotherapy in patients with operable breast cancer and their relationship with response to treatment and prognosis. Patients and Methods: Of 162 patients with stage II/III breast cancer patients receiving neoadjuvant chemotherapy from January 2005 to September 2012 at Keio University Hospital, 140 patients with non-pCR were analyzed. Patients were treated with sequential anthracycline and taxane. ER and PgR were assessed in both CNB performed prior to neoadjuvant chemotherapy and surgical samples. HR status was assessed by immunohistochemistry (IHC). ER/PgR status was determined using the Allred score and defined as positive when score was 3 and more. HR status was considered positive in cases of ER and/or PgR positivity. Pathological response criteria were classified as grade 0, 1, 2, or 3: grade 0 includes almost no change in cancer cells; grade 1 includes slight or marked changes in less than two thirds of area; grade 2 includes marked changes in more than two thirds of area; grade3 includes necrosis or disappearance of all tumor cells. Results: ER, PgR and HR positive rates before neoadjuvant chemotherapy were 72.9%, 67.1% and 76.4%, respectively. Changes in ER, PgR and HR status between CNB and surgical samples were 12.1% (4.3% gain; 7.8% loss), 17.1% (2.1% gain; 15.0% loss) and 9.3% (2.9% gain; 6.4% loss), respectively. In ER-discordant group, grade 2 rate of pathological response was significantly higher than ER- concordant group (61.1% vs. 30%, p=0.033), whereas there were no significant differences of pathological response between discordant and concordant group in PgR status. In the disease free survival (DFS), there were no significant difference between concordance and discordance group for ER, PgR and HR (p=0.216, 0.859, 0.233) after a median follow-up of 40.4 months. But patients with a loss in ER and/or HR status had a trend to a shorter DFS compared with the concordant ER and/or HR-positive group (p=0.169 and 0.154) Conclusions: After neoadjuvant chemotherapy, discordance of biomarkers was seen in 5-20%. The pathological response was significantly associated with the change in ER status. A loss in ER and/or HR status may affect a prognosis of breast cancer after neoadjuvant chemotherapy, but still need further investigation. Citation Format: Toshiaki Kurihara, Hanako Ueno, Masaru Takemae, Aiko Nagayama, Maiko Takahashi, Tetsu Hayashida, Hiromitsu Jinno, Yuko Kitagawa. Prognostic impact of discordance in hormone receptor status after the neoadjuvant chemotherapy in primary breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-06-49.

Change of the hormonal receptor expression in recurred breast cancer

Purpose: Expression of hormone receptors in breast cancer is one of the most important factors in determining its therapeutic plan and prognosis. Various studies have been ongoing regarding resistance in anti-hormone and target therapy of primary and metastatic breast cancers, and hormonal receptor mutation has been pointed out as one of the possible reasons. The purpose of this study was to analyze hormonal receptor changes in primary and metastatic breast cancer patients and to investigate possible influential factors. Methods: Out of 1,620 breast cancer patients who were surgically treated from 1997 to 2013, 38 patients were selected whose tissue samples were adequate for detecting presence of hormonal receptor expression. The presence of estrogen receptor (ER), progesteron receptor (PR), human epidermal growth factor 2 (HER2) receptor mutations were retrospectively analyzed by immunohistochemical staining and fluorescence in-situ hybridization. Results: The positive rate of ER, PR, HER2 receptors were 50%, 47.3%, and 24.3% respectively. In comparison to primary breast cancer, the rate of receptor mutations in recurred and metastatic tissues were 23.6%, 26.3%, and 6.6%; the rate of changes in receptors from positive to negative and negative to positive showed no statistically significant difference. Conclusion: The expression of hormonal receptors in breast cancer tissue is considered as one of the significant factors in pathologic findings, and it is crucial in determining the course of treatment. Recently, performing a tissue biopsy of metastatic lesion in addition to surgically removing the primary cancer has been in trend. Since there are various treatment options for breast cancer including hormonal therapy, chemotherapy, surgery and target therapy, a biopsy of metastatic lesion should be carried out actively in order to increase the specificity of tissue pathology.

Expressions of ER, PR, HER-2, COX-2, and VEGF in Primary and Relapsed/Metastatic Breast Cancers

In the present study, we evaluated expressions of estrogen receptor (ER), progestin receptor (PR), human epidermal growth factor receptor-2 (HER-2), cyclooxygenase-2 (COX-2), and vascular endothelial growth factor (VEGF) in primary and relapsed/metastatic breast cancers to elucidate the clinical significance of these markers. The markers were evaluated by immunohistochemistry in specimens of 50 patients with primary or metastatic breast cancer. Positive rates of ER were significantly (p = 0.002) higher in primary versus relapsed/metastatic breast cancer (70 vs. 38 %, respectively). The VEGF positive expression rates were also significantly higher in primary versus metastatic cancer (82 vs. 38 %, respectively; p < 0.001). By contrast, positive rates of HER-2 and COX-2 were not significantly different between different types of cancer. COX-2 correlated with HER-2 expression in both primary and relapsed/metastatic focuses of breast cancer. COX-2 also correlated with VEGF expression in primary breast cancer. Expressions of ER, PR, HER2, and COX-2 did not correlate between primary and relapsed/metastatic breast cancers, indicating that the treatment decision should be made according to the status of these markers in relapsed/metastatic focuses. The total change rates of ER, PR, HER-2, COX-2, and VEGF were 26, 18, 10, 30, and 58 %, respectively. In conclusion, HER-2 and COX-2, along with VEGF, appear to play a role in the development and progression of breast cancer. In addition, all of the studied markers may serve as indicators of prognosis.

Joint detection of multiple immunohistochemical indices and clinical significance in breast cancer

Breast cancer is one of the most common malignancies in women. This study was conducted to analyze the association between the expressions of eight immunohistochemical (IHC) indices and clinicopathological characteristics in breast cancers (BCs) and investigate the clinical significance. IHC Envision ldpe-g-nvp was used to detect the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), p53, type II topoisomerase (TOPO II) and Ki-67 in postoperative paraffin blocks of 286 cases of invasive BC and statistically analyzed their correlations with clinicopathological characteristics. The positive rates of ER, PR, HER2, VEGF, p53, EGFR, TOPO II and Ki-67 expression were 62.24, 41.96, 57.34, 53.85, 81.82, 46.85, 54.55 and 69.93%, respectively. ER expression was negatively correlated with age, tumor size and histological grade (P<0.05) and PR expression was negatively correlated with age and histological grade (P<0.05). Among the ER, PR and c-erbB-2 statuses, a significant correlation was observed between ER expression and PR status (P=0.0000), whereas the expression of ER and PR exhibited a negative correlation with HER2 status (P<0.05). We also demonstrated a significant correlation between EGFR expression and lymph node metastasis (P=0.0240), p53 expression and tumor size (P=0.0300), p53 and Ki-67 expression and histological grade (P<0.05) and the expressions of VEGF, EGFR, p53, TOPO II, Ki-67 and HER2 status (P<0.05). In addition, the Luminal B and HER2/neu subtypes exhibited a close correlation with age (P<0.01), while the HER2/neu and triple-negative subtypes were positively correlated with poor histological grade (P<0.05). In conclusion, there is a definite correlation between IHC indices and clinicopathological characteristics in BCs. Combined detection of these indices may be significant in the evaluation of biological behavior and prognosis of BC and thus in the diagnosis and comprehensive treatment of this disease.

Analysis on the clinical and prognostic features of 71 male patients with breast cancer

Male breast cancer (MBC) is a rare disease, with clinical and prognostic features still controversial. The aim of this study was to discuss the clinical characteristics and prognosis of MBC. Clinical data related to 71 MBC patients was reviewed. The radio of MBC to female breast cancer (FBC) was 42:10 000. Age related to the diagnosis of MBC ranged from 43 to 84 years with the median age as 62 years old, older than the FBC patients (t = 6.355, P = 0.000). The percentage of invasive ductal carcinoma in MBC patients was much higher than in FBC patients (χ(2) = 29.875, P = 0.000). The positive rate of estrogen receptor (ER) was significantly higher than those in FBC patients and the positive rates of human epidermal growth factor receptor-2 (HER-2) were less frequently (χ(2) = 3.741, P = 0.048 and χ(2) = 12.845, P = 0.002) seen. Data from the univariate and multivariate analysis showed that the 3-, 5- and 10-year survival rates of MBC were 82.6%, 74.0% and 47.4% respectively, significantly higher than those in FBC patients (P = 0.004, P = 0.046). Patients with positive HER-2 showed worse prognosis than HER-2 negative patients in MBC patients (χ(2) = 4.219, P = 0.040). There were significant clinic-pathologic and prognostic differences between FBC and MBC patients. The HER-2 positivity seemed to be an important factor for the prognosis and treatment of patients with MBC.

Response-specific progestin resistance in a newly characterized Ishikawa human endometrial cancer subcell line resulting from long-term exposure to medroxyprogesterone acetate

Progestins, particularly medroxyprogesterone acetate (MPA), have for a long time been used as conservative treatment for young patients with clinical stage I, grade I endometrial carcinoma. However, more than 30% of patients with endometrial adenocarcinoma display resistance to endocrine therapies at the time of presentation and most cancer patients that initially respond to progestin treatment will at some point develop resistance, resulting in tumor progression. The cellular mechanisms underlying acquired resistance to progestin are poorly understood. In order to investigate the molecular mechanisms whereby human endometrial adenocarcinoma develops resistance to progestin therapy, we have undertaken to develop human endometrial adenocarcinoma cell lines that are resistant to the growth-inhibitory effects of progestins in vitro. A progestin-resistant subcell line of Ishikawa cells was developed from Ishikawa human endometrial adenocarcinoma cells by stepwise selection in increasing concentrations of the synthetic progestin, MPA, over ten months. The doubling time of the progestin-resistant cells (34.18±3.15 h) grown routinely in the medium containing 10 μM MPA was not significantly different from the doubling time of the parent Ishikawa cells (35.14±2.68 h) grown in the absence of MPA (t=-0.331, P=0.762). Moreover, the effect of treatment with MPA shifted from suppression of growth and invasiveness, as observed in the parent Ishikawa cells, to stimulation of growth and invasiveness in the progestin-resistant Ishikawa cells. The positive rates of estrogen receptor a (ERα) and progesterone receptor B (PRB) of the progestin-resistant Ishikawa cells were significantly reduced, whilst the positive rate of ERβ was significantly enhanced compared to the parent Ishikawa cells. These differences were statistically significant (P<0.05). Our results indicate that long-term treatment with MPA in Ishikawa cells may give rise to a resistance effect to MPA. When the resistant subtype is acquired, treatment with MPA enhances cancer cell proliferation and invasiveness. The imbalance of ER and PR subtypes may contribute to the mechanisms involved in progestin resistance. Determination of the subtypes of ER and PR may provide important additional information on the hormone sensitivity of endometrial carcinoma.